1224P Systematic review and meta-analysis of immunotherapy effectiveness for pretreated patients with non-small cell lung cancer harboring EGFR exon 20 insertions

Abstract

EGFR exon 20 insertion (ex20ins) mutations are rare, and data on clinical outcomes with immunotherapy (IO) in these patients are scarce. Per National Comprehensive Cancer Network guidelines, IO monotherapy is not recommended over targeted therapies for non–small cell lung cancer (NSCLC) patients with an oncogenic driver. To determine the efficacy of IO monotherapy in the second-line setting and beyond (≥2nd-line) for EGFRex20ins+ NSCLC, we conducted a systematic review and meta-analysis of real-world objective response rate (ORR) data. We analyzed ORRs of ≥2nd-line IO monotherapies in EGFRex20ins+ NSCLC from: (1) PubMed literature search for clinical studies reporting ORR, disease control rate (DCR), or progression-free survival (PFS); (2) longitudinal data from the United States Flatiron Health Research Database; (3) a retrospective chart review from 12 German oncology centers; and (4) prior anticancer therapy and associated response data from a single-arm, phase I/II study of mobocertinib, an oral EGFR tyrosine kinase inhibitor targeting EGFRex20ins, in EGFRex20ins+ NSCLC patients previously treated with ≥2nd-line IO. From the meta-analysis of all data, the calculated ORR [95% confidence intervals] for ≥2nd-line IO monotherapy in patients with EGFRex20ins+ NSCLC was 3.5% [0.6%, 9.9%] (Table). Across sources (N=91), reported ORRs ranged from 0% to 14.3% (1/7 patients in single study), with 2 total responses; DCRs ranged from 23.8% to 30.0%, and median PFS ranged from 2.3 months to 4.0 months. Reported data were limited by small number of patients and studies reporting mixed lines of therapy (≥2nd-line).Table: 1224PData sourceReported ORR, n/N (%)Takeda M. (Oncotarget. 2018)1/7 (14.3%)LC-SCRUM-JAPAN/Udagawa (J Thorac Oncol. 2019)0/21 (0%)Yang G. (Lung Cancer. 2020)0/2 (0%)Flatiron database1/20 (5%)German chart review0/10 (0%)Mobocertinib study0/31 (0%)Meta-analysisMean ORR [2.5%, 97.5%]3.5% [0.6%, 9.9%] Open table in a new tab Results of this meta-analysis suggest that IO monotherapies are not effective in the ≥2nd-line setting for patients with EGFRex20ins+ NSCLC, which further highlights the need for novel treatment options in this population.